Previous work in this laboratory has demonstrated that the vast majority of group A streptococcal strains isolated directly from patients with acute post streptococcal glomerulonephritis (APSGN) excrete a protein of 46,000 daltons. This protein has been labeled the Nephritis Strain Associated Protein (NSAP). Rabbit antisera to purified NSAP indicated that all nephritis associated strains excrete the same protein. Positive immunofluorescent staining with this antiserum was also seen in the glomerular biopsies obtained from 14/21 APSGN patients and was negative in 0/16 patients with non post streptococcal glomerulonephritis. Finally, 95% of patients with APSGN exhibited antibody to purified NSAP while only 15-20% of rheumatic fever patients or impetigo controls exhibited the antibody in their sera. Monoclonal antibodies have been prepared against the NSAP and they demonstrate that in the extracellular products of nephritis strains, two molecular weight bands are present: the original 46,000 M.W. material and a smaller fragment with a M.W. of 40-43,000 daltons. Experiments employing both the polyclonal antisera to streptococcal proteinase as well as the monoclonal NSAP antibody indicate that some NSAP (-) strains do secrete the NSAP early during log phase and these strains also secrete streptococcal proteinase which appears to degrade the original NSAP molecule so that it is no longer detected by the monoclonal antibody. Our present experiments will concentrate on the following areas: 1) isolation and purification of the intact (NSAP) molecule; 2) interaction of NSAP with complement components; 3) biological properties of NSAP in vivo; 4) relationship of the NSAP to streptococcal proteinase and its possible relationship to "nephritogenic" and "non nephritogenic" moieties of the NSAP; 5) the use of the purified NSAP to determine the presence of antibody to NSAP in the general population as well as those who have recovered from the disease. The goal of all these studies is to determine the biological, structural, and immunological properties of the nephritis associated protein.